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WO2018139835A1 - Kit et système esthétique de prévention contre le vieillissement de la peau - Google Patents

Kit et système esthétique de prévention contre le vieillissement de la peau Download PDF

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Publication number
WO2018139835A1
WO2018139835A1 PCT/KR2018/001019 KR2018001019W WO2018139835A1 WO 2018139835 A1 WO2018139835 A1 WO 2018139835A1 KR 2018001019 W KR2018001019 W KR 2018001019W WO 2018139835 A1 WO2018139835 A1 WO 2018139835A1
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Prior art keywords
skin
laser
composition
treatment
kit
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PCT/KR2018/001019
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English (en)
Inventor
Youna SON
Original Assignee
Son Youna
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Priority claimed from KR1020170091989A external-priority patent/KR102048119B1/ko
Application filed by Son Youna filed Critical Son Youna
Priority to CN201880005071.7A priority Critical patent/CN110177541A/zh
Publication of WO2018139835A1 publication Critical patent/WO2018139835A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9706—Algae
    • A61K8/9717—Rhodophycota or Rhodophyta [red algae], e.g. Porphyra
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/0616—Skin treatment other than tanning
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/067—Radiation therapy using light using laser light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/06—Preparations for care of the skin for countering cellulitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/81—Preparation or application process involves irradiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/91—Injection

Definitions

  • the present invention relates to a kit and an aesthetic system for the prevention of skin aging comprising a telomerase activating composition, a skin dermis irradiating laser, a composition for topical fat removal comprising hyaluronidase, and a skin muscle layer irradiating laser, as well as an aesthetic process for preventing skin aging in humans using said kit and system.
  • Extrinsic skin aging results in the formation of wrinkles on the skin.
  • Typical factors causing wrinkling include accumulation of fat, loss of subcutaneous muscles, reactive oxygen species, UV light, reduction of collagen biosynthesis, etc. That is, external physical or chemical factors, for example, heat, intense UV, physical abrasion (injury), acidic substances, etc. cause the destruction of skin tissues, which in turn causes the destruction of underlying collagen or elastin structures, gelatin, or the like, leading to the formation of wrinkles.
  • collagen is a major matrix protein produced by fibroblasts in the skin and found in the extracellular matrix, is an important protein that accounts for 30% of the total body protein weight, and has a robust triple helical structure.
  • Major functions of collagen have been reported to include maintenance of the mechanical firmness of the skin, the cohesion and resistance of the connective tissue, maintenance of the adhesion of cells, and inducement of cellular division and differentiation.
  • Collagen is known to degrade in proportion to the accumulated exposure time to UV light. Thus, external factors such as UV light lead to the accumulation of elastic material and denaturation of collagen fibers in the skin dermis, resulting in the formation of wrinkles and reduction of elasticity in the skin.
  • extrinsic skin aging is easier to control, compared to intrinsic skin aging, e.g., by the removal of reactive oxygen species, proliferation of fibroblasts, and stimulation of collagen biosynthesis.
  • important functions of collagen in the skin are being identified.
  • Newly emerging wrinkle treatments include ultrasound treatment, skin scaling, laser peel, botulinum toxin injection, or the like. However, they are still unsatisfactory in terms of treatment effect and duration.
  • telomeres at the ends of chromosomes function to buffer the loss of genetic information in the form of shortening of DNA due to the DNA replication mechanism for cell division.
  • chromosomes With each round of cell division, chromosomes lose a certain length of DNA.
  • telomeres With each round of cell division, chromosomes lose a certain length of DNA.
  • telomeres Upon exceeding a certain number of cell divisions, telomeres become too shortened, eventually leading to the termination of cell division followed by cell death.
  • telomeres have a prolonged life span if telomeres are kept long, which can be done by the enzyme telomerase.
  • research on telomerases is ongoing as a strategy to prevent the genetic aging of cells.
  • Patent Literature 1 Korean Patent Publication No. 10-2014-0146074 (December 24, 2014).
  • the present invention is intended to address the above-mentioned problems. It is an object of the present invention to provide a kit and an aesthetic system for the prevention of skin aging utilizing the stimulation of collagen formation, stimulation of telomerase activity, recovery from loss of elasticity due to skin aging, wrinkle improvement, degradation of undesired fat layers, and skin contouring, as well as an aesthetic process for preventing skin aging in humans using said kit and system, for the comprehensive prevention of skin aging that can prevent or delay extrinsic skin aging as well as intrinsic skin aging.
  • the present inventor endeavored to develop a system for the prevention of skin aging by utilizing the stimulation of collagen formation, stimulation of telomerase activity, recovery from loss of elasticity due to skin aging, wrinkle improvement, degradation of undesired fat layers, and skin contouring and has discovered that the kit and aesthetic system for the prevention of skin aging of the present invention comprising a telomerase activating composition, a skin dermis irradiating laser, a composition for topical fat removal comprising hyaluronidase, and a skin muscle layer irradiating laser has the effect of comprehensive prevention of skin aging that can prevent or delay extrinsic skin aging as well as intrinsic skin aging.
  • the present invention comprises compositions and light sources (lasers) with certain frequencies that prevent skin aging by comprehensively preventing intrinsic skin aging due to genetic factors and extrinsic skin aging due to various factors and rejuvenating aged skin.
  • the prevention of skin aging includes stimulating collagen production, inducing collagen contraction and remodeling, contouring of sagging skin resulting from the loss of elasticity and accumulation of fat, enhancing skin elasticity, and improving wrinkles.
  • the prevention of skin aging also includes removing or reducing undesirably accumulated topical fat, lipolysis in adipose cells, reducing edema, preventing or delaying intrinsic skin aging by activating telomerases in skin cells.
  • the prevention of skin aging further includes improving skin hydration, improving skin roughness, and improving skin tone by improving pigmentation. That is, the prevention of skin aging in the present invention refers to, but is not limited to, improving or preventing one or more of the skin aging symptoms listed above.
  • A) a telomerase activating composition, B) a skin dermis irradiating laser, C) a composition for topical fat removal, and D) a skin muscle layer irradiating laser consisting the kit and aesthetic system for the prevention of skin aging according to the present invention, as well as treatment processes using the same will be explained in detail.
  • telomerase refers to an enzyme that maintains the length of telomeres, the genetic material made of repetitive nucleotide sequences found at the ends of chromosomes, thereby serving to prevent cellular senescence. Telomeres protect chromosomes from damage or fusion with other chromosomes, and their length shortens with each round of cell division. Upon exceeding a certain number of cell divisions, telomeres become too short, leading to the termination of cell division followed by cell death.
  • telomerase is an enzyme that serves to maintain cells at the pre-senescence stage by preventing the loss of cellular genetic material and genetic information.
  • cellular senescence is prevented by using a telomerase activating composition that activates telomerase (increases the expression of telosome proteins) and keeps the telomere length long.
  • any composition that can activate telomerases may be used as the telomerase activating composition.
  • the telomerase activating composition of the present invention is characterized in that it increases the expression of telosome subunit proteins in skin cells and/or maintains the telomere length of chromosomes in skin cells.
  • the telosome subunit protein refers to one or more selected from TRF1 (Telomeric Repeat Factor 1), TRF2 (Telomeric Repeat Factor 2), RAP1 (Repressor Activator Protein 1), TIN2 (TERF1-interacting nuclear factor 2), POT1 (Protection of telomeres 1), and TPP1 (Tripeptidyl peptidase 1).
  • the telomerase activating composition of the present invention comprises Dendropanax morbifera Lev. extract, Kappaphycus alvarezii extract, or their mixture as the active ingredient.
  • the Dendropanax morbifera Lev. extract or Kappaphycus alvarezii extract of the present invention can be prepared by grinding Dendropanax morbifera Lev. bark or Kappaphycus alvarezii followed by precipitation in a solvent (water, C 1 to C 6 alcohol or organic solvent such as ethanol, methanol, hexane, etc.) and treatment with a hydrolytic enzyme to obtain the extract, but are not limited thereto.
  • a solvent water, C 1 to C 6 alcohol or organic solvent such as ethanol, methanol, hexane, etc.
  • a telomerase activating composition may contain the active ingredient Dendropanax morbifera Lev. extract or Kappaphycus alvarezii extract in an amount of 0.00001 to 10%(w/w), 0.0001 to 5%(w/w), or 0.001 to 3%(w/w).
  • a telomerase activating composition can be formulated using conventional carriers, diluents or excipients such as lubricants, humectants, flavors, emulsifiers, suspending agents, preservatives, surfactants, etc.
  • the telomerase activating composition is a topical preparation. Specifically, it can be formulated as an essence, treatment, serum, emulsion, cream, ampule, lotion or pack, but is not limited thereto.
  • the above composition may include, in addition to the active ingredient Dendropanax morbifera Lev. extract or Kappaphycus alvarezii extract, anti-oxidants, stabilizers, solubilizers, vitamins, pigments, fragrances or the like that are commonly used in respective formulations.
  • Examples of said carriers, diluents and excipients include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, alginate, gelatin, calcium silicate, polyvinylpyrrolidone, cellulose, water, syrup, methyl hydroxybenzoate, propyl hydroxybenzoate, xanthan gum, talc, magnesium stearate, mineral oil, etc.
  • the telomerase activating composition of the present invention is a cosmetic composition, and can further comprise substances that are well known in the field of cosmetic compositions to have a useful effect on the skin.
  • Viscum album extract, Imperata cylindrica root extract, soybean extract, and the like can be additionally included.
  • Individual extracts of the present invention may be extracts fermented by microorganisms such as yeast or lactobacillus, but are not limited thereto.
  • telomerase activating composition of the present invention As a preparation example for the telomerase activating composition of the present invention, an ampule and a cream containing 0.00056%(w/w) of Kappaphycus alvarezii extract were prepared (Table 1 and Table 2).
  • the amount of the telomerase activating composition of the present invention to be applied to the skin varies according to the skin condition, formulation of the composition, time of application, or the like, but can be suitably selected by a person skilled in the art. Specifically, a single dose of the composition is 3 to 20 cc, and the composition can be applied 1 to 5 times daily as needed.
  • application of the telomerase activating composition may be accompanied by a treatment with an ultrasound laser having a frequency of 10 to 90Hz.
  • accompanying treatment means that the treatment with an ultrasound laser is carried out simultaneously with or immediately after the application of the telomerase activating composition, with the irradiation lasting for 5 to 20 minutes.
  • an ultrasound laser having a frequency of 30 Hz is irradiated for 10 minutes after 10 cc of a telomerase activating composition is applied to the skin.
  • the skin dermis irradiating laser of the present invention is a laser having a frequency of 2 to 100 Hz or an RF (Radio Frequency) laser, and delivers heat energy to the dermis or to the dermis and SMAS (Superficial Musculoaponeurotic System).
  • the skin dermis irradiating laser of the present invention may be one or more lasers. For example, it is one or more lasers selected from the group consisting of [a laser having a frequency of 2 to 9 Hz], [a laser having a frequency of 30 to 50 Hz] and [an RF (35 MHz to 45 MHz) laser].
  • the irradiation time can be, but is not limited to, 1 to 10 minutes.
  • the skin dermis irradiating laser having a frequency of 30 to 50 Hz works to deliver the laser energy (heat energy of 65 °C) to the deep dermis and SMAS using high intensity focused ultrasound (HIFU).
  • This causes contraction of the muscle layer under the dermis, resulting in the reduction of wrinkles, and helps the production of collagen and elastin.
  • this laser helps lipolysis if there are excessive fat layers.
  • This laser can be operated in two different modes according to the depth reached by the laser wave. In one mode, the laser wave reaches 3.5 mm deep under the skin surface and contracts the dermal layers, thereby reducing wrinkles and stimulating collagen and elastin production.
  • the laser wave In the other mode, the laser wave reaches 4.5 mm deep under the skin surface, helping the lipolysis of fat layers in the skin.
  • Treatments can include either one of the above two modes, or both modes.
  • the irradiation time can be 10 to 40 minutes respectively, but is not limited thereto.
  • a 92 W RF laser (35 MHz to 45 MHz) used in the present invention allows the RF wave to penetrate the skin dermis/fat layers, generating heat deep in the dermis and thereby inducing tissue contraction and reorganization.
  • the laser generates heat in the connective tissue, blood flow and circulation increase, resulting in tissue firming and improved skin texture. It is also an effect of this laser that intercellular water and noxious substances are discharged, resulting in a visible slimming of the skin contour in the irradiated area.
  • This laser can be irradiated for 3 to 10 minutes in the unipolar mode, but is not limited thereto.
  • the laser of the present invention to deliver energy to the deep dermis can be selected from the above three types of laser. It may be any combination selected from the above three types of laser, or all three types of laser may be used together.
  • a laser with a wavelength of 1064 nm and a frequency of 5Hz (GentleMax) was irradiated for 3 or 5 minutes, and then Indigo laser with a frequency of 30 to 50 Hz was irradiated in mode A (laser wave reaches 3.5 mm deep under the skin surface) and mode B (laser wave reaches 4.5 mm deep under the skin surface) for 10 or 20 minutes, respectively.
  • the skin was irradiated with an RF laser having a frequency of 40.68 MHz for 6 minutes.
  • the skin dermis irradiating laser of the present invention can bring about one or more of the following changes:
  • composition for topical fat removal of the present invention comprises 300 IU to 600 IU of hyaluronidase per single dose volume, and may further comprise one or more of a local anesthetic, an antihistamine, a lipolysis stimulator and a collagen production stimulator.
  • Hyaluronidase is a water-soluble enzyme secreted from a mammalian vas deferens or testes, characterized by its actions to remove barriers between tissues by hydrolyzing the glucosaminic bonds between hyaluronic acid, a major intercellular substance, and connective tissues to dissolve the bonds and reduce fibroplasia in tissues. Hyaluronidase is also known to relieve swelling and edema in tissues.
  • LLD Lipolytic Lymph Drainage
  • LLD treatments using high doses of hyaluronidase cause allergic symptoms such as redness or itching, and excessive lysis of adipose tissue leads to bruising due to subcutaneous bleeding or dimpling.
  • LLD treatments have drawbacks that treatment has to be discontinued frequently to take care of such side effects and continuous treatment is difficult due to patients' repulsion due to pain.
  • the present inventor discovered that the minimum amount of hyaluronidase exhibiting efficacy is 300 IU and that above 600 IU, adipose cells are excessively hydrolyzed, causing concerns about dimpling or subcutaneous bleeding.
  • the single dose of hyaluronidase in the injection composition for topical fat removal of the present invention to 300 IU to 600 IU, the side effects from using the drug are minimized and yet fat removal over a wide area can be carried out using a minimal volume.
  • the diameter of the diffusion range for the injection composition is about 1 cm.
  • the injection composition of the present invention is injected to give 300 IU to 600 IU of hyaluronidase per injection, at a single dose volume of 0.5 to 2 cc with an interval between injection points of 0.5 to 1.5 cm.
  • the daily dose of hyaluronidase is preferably 15,000 IU or less, and the single dose volume and injection points can be suitably adjusted according to the IU of hyaluronidase.
  • the injection composition of the present invention can be injected 50 times on a fixed interval based on an injection volume of 1 cc containing 300 IU of hyaluronidase, and the site of injection can be any body area where fat is accumulated including abdomen, buttocks, thighs, calves, chin, forehead, arms, and the like.
  • the injection composition of the present invention may also comprise a local anesthetic to alleviate the pain from injection, an antihistamine to prevent allergic side effects, a lipolysis stimulator to rapidly transport fatty acids from degraded fat into mitochondria and degrade them, and a collagen stimulator.
  • a local anesthetic to alleviate the pain from injection
  • an antihistamine to prevent allergic side effects
  • a lipolysis stimulator to rapidly transport fatty acids from degraded fat into mitochondria and degrade them
  • a collagen stimulator a collagen stimulator.
  • lidocaine can be used in an amount of 0.08 to 0.4 % by weight based on the total weight of the composition.
  • analgesic effect is unsatisfactory, and when the amount is above 0.4%, the duration of anesthesia is prolonged and is uneconomical.
  • the antihistamine Peniramin pheniramine
  • the lipolysis stimulator L-carnitine in an amount of 0.01 to 4.0 % by weight
  • the collagen synthesis stimulator vitamin C in an amount of 0.1 to 2.0 % by weight.
  • composition of the present invention may also comprise one or more substances selected from a tonicity agent, a nonionic surfactant, a stabilizer, a preservative, etc. that are commonly used in injectable solutions, within dose ranges allowable for injection compositions.
  • the composition of the present invention may further comprise a lipolytic agent such as phosphatidylcholine, aminophylline, caffeine, or the like as well as placenta components or pentoxifylline which improves blood circulation, in amounts of 0.01 to 4.0 % by weight.
  • the injection composition for topical fat removal of the present invention, comprises 300 IU to 600 IU of hyaluronidase per single dose volume and, based on the weight of the total composition, 0.08 to 0.4 % by weight of lidocaine as local anesthetic, 0.01 to 0.02 % by weight of Peniramin as antihistamine, 0.01 to 4.0 % by weight of L-carnitine as lipolysis stimulator, and 0.1 to 2.0 % by weight of vitamin C as collagen synthesis stimulator, with the remainder being saline solution, and the composition is injected at a volume of 0.5 to 2 cc per single dose with an interval between injection points of 0.5 to 1.5 cm.
  • the skin muscle layer irradiating laser of the present invention is irradiated from inside the mouth toward the face and is a laser having a frequency of 1 to 3.5 Hz which delivers energy to the skin muscle layer.
  • this laser delivers energy to the muscle layer, it has excellent effects on collagen synthesis, wrinkle improvement, and elasticity enhancement. Particularly, it can effectively deliver energy to the skin muscle layer by irradiating the laser beam from inside the mouth toward the face.
  • this laser treatment is painless, and provides a thermal effect to the oral mucosa in a non-ablative, non-invasive manner without anesthesia to give a remodeling and tightening effect.
  • the intraoral treatment of this step applies a laser beam delivering controlled energy such that a temperature in the range of from 45 to 70°C, or from 45 to 65°C, is reached in the upper dermis, which can lead to an instantaneous contraction of 30% of the tissue.
  • the instantaneous contraction of the upper dermis mechanically pulls up the underlying deeper tissue layers, creating a lifting effect.
  • this laser treatment delivers energy through the oral mucosa, it can protect the epidermis and stimulate collagen remodeling and neo-collagenesis (lasting up to 6 months).
  • this laser treatment has the advantage that it is accompanied by no bleeding or pain except some warmth felt in the oral mucosa and it does not affect the daily life after the treatment since oral mucosa is particularly quick to recover.
  • a skin muscle layer irradiating laser with a frequency of 1.8 Hz or 3 Hz was irradiated from inside the mouth toward the face for 5 or 6 minutes.
  • the skin muscle layer irradiating laser of the present invention can bring about one or more of the following changes:
  • the present invention provides in one aspect a kit for the prevention of skin aging, comprising A) a telomerase activating composition; B) a skin dermis irradiating laser; C) a composition for topical fat removal comprising 300 IU to 600 IU of hyaluronidase; and D) a skin muscle layer irradiating laser.
  • kits for the prevention of skin aging according to the present invention may further comprise an ultrasound laser having a frequency of 10 to 90 Hz that is applied simultaneously with or immediately after the application of the telomerase activating composition.
  • treatments with the above elements A) to D) may be carried out irrespective of their order, e.g., in the order stated, in an inverse order, or in a random order.
  • the kit of the present invention may be used in the order of [A), B), C) and D)], [A), B), D) and C)], [A), C), D), and B)], [A), D), B), and C)], [A), D), B), and C)], [A), D), C), and B)], [B), A), C), and D)], [B), A), D), and C)], [B), A), D), and C)], [B), D), A), and D)], [B), D), A), and C)], [B), D), C), and A)], [C), A), B), and D)], [C), B), A), and D)], [C), B), A), and D)], [C), B), D), and A)], [C), B), D), and A)], [C), B), D), and A)], [C), D), B), and A)], [C), D), B), and A)], [C), D), B), and A)], [C), D), B), and A)
  • kit of the present invention may be repeatedly used in 1 to 10 cycles, but is not limited thereto. In each cycle, treatments with the above elements A) to D) may be carried out irrespective of their order.
  • the present invention provides an aesthetic system for the prevention of skin aging, comprising A) a telomerase activating composition; B) a skin dermis irradiating laser; C) a composition for topical fat removal comprising 300 IU to 600 IU of hyaluronidase; and D) a skin muscle layer irradiating laser.
  • telomerase The telomerase, the telomerase activating composition, the skin dermis irradiating laser, hyaluronidase , the composition for topical fat removal comprising 300 IU to 600 IU of hyaluronidase, and the skin muscle layer irradiating laser of the present invention are as described above.
  • the aesthetic system according to the present invention may further comprise an ultrasound laser having a frequency of 10 to 90 Hz that is applied simultaneously with or immediately after the application of the telomerase activating composition.
  • the aesthetic system of the present invention comprises the following elements.
  • treatments with the following elements may be carried out irrespective of their order, e.g., in the order stated, in an inverse order, or in a random order:
  • telomerase activating composition to be applied to the skin
  • a skin dermis irradiating laser to be irradiated on the skin for 3 to 60 minutes;
  • composition for topical fat removal to be injected at a single dose volume of 0.5 to 2 cc with an interval between injection points of 0.5 to 1.5 cm;
  • the aesthetic system of the present invention may further comprise irradiating an ultrasound laser having a frequency of 10 to 90 Hz for 5 to 20 minutes simultaneously with or immediately after the treatment with element i).
  • the aesthetic system of the present invention may be used in the order of [i), ii), iii), and iv)], [i), ii), iv), and iii)], [i), iii), ii), and iv)], [i), iii), iv), and ii)], [i), iv), ii), and iii)], [i), iv), iii), and ii)], [ii), i), iii), and iv)], [ii), i), iv), and iii)], [ii), iii), i), and iv)], [ii), iv), i), and iii)], [ii), iv), i), and iii)], [ii), iv), i), and iii)], [ii), iv), i), and iii)], [ii), i
  • the skin dermis irradiating laser in ii) above is one or more lasers selected from the group consisting of a laser having a frequency of 5 Hz, a laser having a frequency of 30 to 50 Hz and an RF laser.
  • the laser having a frequency of 5 Hz may be irradiated for 3 to 8 minutes, and the laser having a frequency of 30 to 50 Hz for 15 to 40 minutes.
  • the RF laser may be irradiated for 4 to 10 minutes with a frequency of 40.68 MHz.
  • the aesthetic system of the present invention may be repeatedly used in 1 to 10 cycles, but is not limited thereto.
  • treatments with the above elements i) to iv) may be carried out irrespective of their order.
  • treatments with elements i), ii), iii), and iv) may be carried out in the order stated with an interval of one week, and with this entire process considered as one cycle, the treatments can be repeated for three cycles.
  • telomerase activating composition containing 0.00056%(w/w) of Kappaphycus alvarezii extract was applied, followed by irradiation with an ultrasound laser having a frequency of 30 Hz for 10 minutes.
  • an ultrasound laser having a frequency of 30 Hz for 10 minutes.
  • a laser having a frequency of 5Hz (GentleMax) was irradiated for 5 minutes
  • Indigo laser a laser having a frequency of 30 to 50 Hz, was irradiated in mode A and mode B for 20 minutes respectively, followed by irradiation with an RF laser with a frequency of 40.68 MHz for 6 minutes.
  • a composition for topical fat removal comprising 30,000 IU to 60,000IU of hyaluronidase, 210 mg of lidocaine, 12 mg of Peniramin, 660 mg of L-carnitine, and 600 mg of vitamin-C
  • a single dose volume of 1 cc each was injected at 50 points with an interval between injection points of 1 cm, four times with an interval of one week.
  • a skin muscle layer irradiating laser having a frequency of 1.8 Hz or 3 Hz was irradiated from inside the mouth toward the face for 5 minutes.
  • 3 cc of a telomerase activating composition containing 0.00056%(w/w) of Kappaphycus alvarezii extract was applied, followed by irradiation with an ultrasound laser having a frequency of 30 Hz for 10 minutes.
  • an ultrasound laser having a frequency of 30 Hz for 10 minutes.
  • a laser having a frequency of 5Hz (GentleMax) was irradiated for 3 minutes
  • Indigo laser a laser having a frequency of 30 to 50 Hz, was irradiated in mode A and mode B for 10 minutes respectively, followed by irradiation with an 90w RF laser in the unipolar mode for 6 minutes.
  • 100 cc of a composition for topical fat removal comprising 30,000 IU to 60,000 IU of hyaluronidase, 210 mg of lidocaine, 12 mg of Peniramin, 660 mg of L-carnitine, and 600 mg of vitamin-C was prepared and a single dose volume of 1 cc each was injected at 10 points with an interval between injection points of 1 cm. Thereafter, a skin muscle layer irradiating laser having a frequency of 3 Hz was irradiated from inside the mouth toward the face for 6 minutes.
  • the present invention provides an aesthetic process for preventing skin aging using the kit and aesthetic system for the prevention of skin aging according to the present invention.
  • kit and aesthetic system for the prevention of skin aging according to the present invention are as described above.
  • the present invention provides an aesthetic process for the prevention of skin aging, wherein the following steps are carried out at least once irrespective of their order:
  • telomerase activating composition i) a step of applying a telomerase activating composition
  • ii) a step of irradiating a skin dermis irradiating laser for 3 to 60 minutes;
  • a step of injecting a composition for topical fat removal at a single dose volume of 0.5 to 2 cc with an interval between injection points of 0.5 to 1.5 cm;
  • iv a step of irradiating a skin muscle layer irradiating laser from inside the mouth toward the face for 3 to 10 minutes.
  • the aesthetic process of the present invention may further comprise irradiating an ultrasound laser having a frequency of 10 to 90 Hz for 5 to 20 minutes simultaneously with or immediately after step i).
  • the above steps may be carried out irrespective of their order, e.g., in the order stated, in an inverse order, or in a random order.
  • the above steps may be carried out in the order of [i), ii), iii), and iv)], [i), ii), iv), and iii)], [i), iii), ii), and iv)], [i), iii), iv), and ii)], [i), iv), iii), and ii)], [ii), i), iii), and iv)], [ii), i), iii), and iv)], [ii), i), iv), and iii)], [ii), i), iv), and iii)], [ii), i), i), and iv)], [ii), i), i), and iv)], [ii), iii),
  • the above steps i) to iv) may be carried out by the same person, and suitable time intervals may be placed between the steps.
  • the suitable time interval between the steps may be 1 to 60 minutes, 1 to 24 hours, or 1 day to 2 weeks, depending on the skin condition and the preparation time for the next treatment.
  • the time interval can be determined by those skilled in the art and may vary according to the treatment step and skin condition.
  • the skin dermis irradiating laser in step ii) of the present invention is one or more lasers selected from the group consisting of a laser having a frequency of 5 Hz, a laser having a frequency of 30 to 50 Hz and an RF laser.
  • the laser having a frequency of 5 Hz may be irradiated for 3 to 8 minutes, and the laser having a frequency of 30 to 50 Hz for 15 to 40 minutes.
  • the RF laser may be irradiated for 4 to 10 minutes with a frequency of 40.68 MHz.
  • the kit and aesthetic system for the prevention of skin aging according to the present invention have comprehensive effects concerning skin aging including instantaneous wrinkle improvement, skin contouring, elasticity enhancement, wrinkle improvement, topical fat removal, and skin hydration improvement as well as long-lasting maintenance effects up to 1 year to 1.5 years, despite their short treatment time.
  • the present invention has excellent effects in terms of preventing skin aging.
  • FIG. 1 illustrates the expression of the telosome proteins POT1 and TPP1 in fibroblasts treated with 0.25% or 0.5% Kappaphycus alvarezii extract after induction of senescence with H 2 O 2 .
  • FIG. 2 illustrates the telomere length in fibroblasts treated with 0.25% or 0.5% Kappaphycus alvarezii extract after induction of senescence with H 2 O 2 .
  • FIG. 3 shows photographs illustrating the extent of senescence determined using a ⁇ -galactosidase staining kit (Sigma Senescent cell staining kit) in fibroblasts treated with 0.25% or 0.5% Kappaphycus alvarezii extract after induction of senescence with H 2 O 2 .
  • FIG. 4 shows the extent of senescence measured by a confocal microscope on the starting day and Day 42 in a clinical study to verify the preventive effect of a composition comprising Kappaphycus alvarezii extract on skin aging.
  • FIG. 5 shows the extent of senescence measured by a 3D scanner on the starting day and Day 42 in a clinical study to verify the preventive effect of a composition comprising Kappaphycus alvarezii extract on skin aging.
  • FIG. 6 shows the results of the perception tests to gauge the age of subjects on the starting day and Day 42 in a clinical study to verify the preventive effect of a composition comprising Kappaphycus alvarezii extract on skin aging.
  • FIG. 7 is photographs of skin contours showing enhanced elasticity in the double chin and cheek areas immediately after irradiation with a skin dermis irradiating laser.
  • FIG. 8 is photographs of nasolabial wrinkles after 1 session of treatment with a skin muscle layer irradiating laser.
  • FIG. 9 shows the number of collagen fibers measured in skin biopsies taken from 90 subjects grouped into a test group and Controls 1 to 8 at baseline as well as 1 week, 2 weeks, 3 weeks and 4 weeks post-treatment to comprehensively investigate the effects of the kit and aesthetic system for the prevention or treatment of skin aging according to the present invention.
  • the test group representing the present invention, was treated with A) a telomerase activating composition, B) a skin dermis irradiating laser, C) a composition for topical fat removal, and D) a skin muscle layer irradiating laser, while the control groups received only some of the treatments.
  • Control 1 received treatment A; Control 2 treatment B; Control 3 treatment C; Control 4 treatment D; Control 5 treatments A, B, and C; Control 6 treatments A, B, and D; Control 7 treatments A, C, and D; Control 8 treatments B, C, and D.
  • FIG. 10 shows the skin elasticity improvement measured in the subjects in the test group and Controls 1 to 8 at baseline as well as 1 week, 2 weeks, 3 weeks and 4 weeks post-treatment.
  • a DermaLab USB elasticity probe (Cortex Technology, Inc.) was employed to assess the changes in skin elasticity.
  • FIG. 11 shows the wrinkle improvement effect determined by measuring the wrinkling in the subjects in the test group and Controls 1 to 8 at baseline as well as 1 week, 2 weeks, 3 weeks and 4 weeks post-treatment.
  • a device quantifying the extent of wrinkling (Aramo TS, programmed by Aram HUVIS Co., South Korea) was used to assess the changes in wrinkling.
  • FIG. 12 shows the facial contouring effect measured in the subjects in the test group and Controls 1 to 8 at baseline as well as 1 week, 2 weeks, 3 weeks and 4 weeks post-treatment.
  • a SuperSonic Imagine (Les Jardins de la Duranne, Aix en Brussels, France) ultrasound, which measures the thickness of subcutaneous fat in the face area, was used for the assessment.
  • FIG. 13 shows the telomerase activating effect measured in the subjects in the test group and Controls 1 to 8 at baseline as well as 1 week, 2 weeks, 3 weeks and 4 weeks post-treatment. Blood samples from the subjects were analyzed by sandwich enzyme immunoassay to measure the amount of telomerase.
  • FIG. 14 shows the skin hydration improvement measured in the subjects in the test group and Controls 1 to 8 at baseline as well as 1 week, 2 weeks, 3 weeks and 4 weeks post-treatment. Skin hydration was determined by measuring the capacitance reflecting the water content, which has the highest dielectric constant in the skin.
  • FIG. 15 shows the skin roughness improvement determined by measuring skin roughness in the subjects in the test group and Controls 1 to 8 at baseline as well as 1 week, 2 weeks, 3 weeks and 4 weeks post-treatment. Images of the test areas were taken using a Beauty scope (X 60 lens) with a diameter of 30 mm, and the skin surface contour was transformed into a graph and numbers to obtain skin roughness values.
  • Beauty scope X 60 lens
  • FIG. 16 shows the changes in the amount of pigmentation measured in the subjects in the test group and Controls 1 to 8 at baseline as well as 1 week, 2 weeks, 3 weeks and 4 weeks post-treatment.
  • a RSA Robot Skin Analyzer CS 50, In Forward. Inc., Japan
  • a Kappaphycus alvarezii extract was used to prepare a telomerase activating composition. Specifically, Kappaphycus alvarezii was ground and then precipitated in a solvent (water, C 1 to C 6 alcohol or organic solvent such as ethanol, methanol, hexane, etc.), followed by the addition of a hydrolytic enzyme to obtain an extract.
  • a solvent water, C 1 to C 6 alcohol or organic solvent such as ethanol, methanol, hexane, etc.
  • a human fibroblast cell line was placed in a 100-mm plate (Corning 100 mm TC-Treated Culture Dish, Product #430167) at a concentration of 1800 cells/cm 2 and treated with a fibroblast medium containing a Kappaphycus alvarezii extract at a final concentration of 0.25% or 0.5%. Then, senescence was induced by treating with H 2 O 2 (hydrogen peroxide 4 x 40 uM) for 96 hours.
  • H 2 O 2 hydrogen peroxide 4 x 40 uM
  • telomere length of telomeres and the expression of telosome proteins in the groups were compared.
  • telosome proteins working to protect and maintain the length of telomeres was maintained high in the test groups treated with a Kappaphycus alvarezii extract. Particularly, expression of the above proteins was maintained at a level close to that in normal pre-senescent fibroblasts when the cells were treated with a Kappaphycus alvarezii extract at a concentration of 0.5%. In contrast, the expression of the above two proteins was reduced to 68% and 82%, respectively, in fibroblasts aged by induction of senescence without a treatment with a Kappaphycus alvarezii extract (FIG. 1).
  • telomere shortening results showed that treatment with a Kappaphycus alvarezii extract at a concentration of 0.5% could inhibit about 65% of telomere shortening resulting from senescence (FIG. 2).
  • senescence Stage 1 denotes the most senescent state and Stage 4 refers to young skin with the least progressed senescence.
  • test group showed an ameliorated extent of skin aging at Day 42 relative to Day 0 compared to the placebo group, as illustrated by FIG. 4. 58% of the subjects in the test group showed an improvement in their skin stage, and 46% of those subjects showed an improvement from senescence Stage 1 or 2 to Stage 3 or 4.
  • FIG. 5 illustrates the measurements of wrinkle depth in the ocular area, showing that the wrinkle depth improved 27.9% at Day 42 relative to Day 0.
  • Reference Example 2 Accompanying treatment with a telomerase activating composition and an ultrasound laser
  • the Kappaphycus alvarezii extract obtained in Reference Example 1 was used for the preparation of a telomerase activating composition. Specifically, a telomerase activating composition comprising the Kappaphycus alvarezii extract prepared in Reference Example 1 was formulated into a cream and an ampule having the composition shown below.
  • composition of the telomerase activating cream Ingredients Content % (w/w) Glycerin 8.0 Sunflower seed oil 3.2 Stearic acid 2.5 Mango seed butter 1.5 Kappaphycus alvarezii extract 0.0056 Yeast/ Viscum album extract fermented 0.007 Lactobacillus / soybean extract fermented 0.0036 Yeast/ Imperata cylindrica root extract fermented 0.0026 Purified water q.s.
  • composition of the telomerase activating ampule Ingredients Content % (w/w) Glycerin 22.0 Sodium PCA 12.0 Xanthan gum 0.2 Citric acid 0.15 Kappaphycus alvarezii extract 0.0056 Yeast/ Viscum album extract fermented 0.007 Lactobacillus / soybean extract fermented 0.0036 Yeast/ Imperata cylindrica root extract fermented 0.0026 Purified water q.s.
  • telomerase activating composition in the form of a topical preparation was applied to the skin of the 24 test group subjects in Reference Example 1, an ultrasound laser with a frequency of 10 to 90 Hz was irradiated to facilitate the delivery of the composition into the skin.
  • telomerase activating composition in the form of a topical preparation was applied to the skin, a laser (Legato - Alma Lasers, Israel; and Sonopact - Medius, South Korea) set at a frequency of 30 Hz was irradiated for 10 minutes over the entire face area in 1 to 2 passes.
  • a laser Legato - Alma Lasers, Israel; and Sonopact - Medius, South Korea
  • the ultrasound laser i) had a vibration effect (hammering-impact effect; push-pull effect) on the treated skin area, and ii) caused a thermal effect resulting from vibration in the epidermal tissue and the dermis.
  • iii) destroyed degenerated keratinocytes resulting from ultrasound application, and effectively delivered the composition to the dermis by facilitating the composition to penetrate into the intercellular spaces.
  • a laser having a wavelength of 1064 nm and a frequency of 5 Hz was irradiated on the skin surface for 5 minutes so that the laser energy penetrates deep into the dermis to deliver heat energy.
  • a laser having a frequency of 30 to 50 Hz (Indigo-K1MED, South Korea) delivered the laser energy (heat energy of 65°C) to the deep dermis and SMAS using high intensity focused ultrasound (HIFU).
  • This laser has mode A and mode B, and the treatment consisted of irradiation in mode A and mode B for 20 minutes each. This caused contraction of the muscle layer under the dermis, resulting in reduction of wrinkles and stimulation of collagen and elastin production.
  • this laser irradiation induced lipolysis if there are excessive fat layers at a depth of 10 to 20 mm.
  • a 92 W RF laser (40.68 MHz; Tenor Laser-Alma lasers, Israel) was irradiated in the unipolar mode for 6 minutes. This allowed the RF wave to penetrate the skin dermis/fat layers and generate heat deep in the dermis, inducing tissue contraction and reorganization. As the laser generated heat in the connective tissue, blood flow and circulation increased, resulting in tissue firming and improved skin texture. Also, intercellular water and noxious substances were discharged, resulting in a visible slimming of the skin contour in the irradiated area.
  • Reference Example 4 A composition for topical fat removal comprising a hyaluronidase and its lipolytic effect
  • composition for topical fat removal comprising a hyaluronidase was administered to 40 (20 male and 20 female) volunteers selected from patients having abdominal obesity with a BMI of 25 or greater among adults of age 20 or above, in the form of injection given to their abdomen area.
  • the effects of the composition for topical fat removal according to the present invention were determined as described below.
  • the Liporase Inj. of Daehan New Pharm Co., Ltd (1500 IU/vial, containing 13.3 mg lactose hydrate) was used, to which lidocaine (Hanmi Pharm. Co., Ltd.), Peniramin (Yuhan Co.), L-carnitine (Dream Pharma) and vitamin-C (Daewoo Pharm Co., Ltd.) were added in the amounts listed in the following table and mixed well to prepare 100 cc of a solution composition for injection.
  • compositions for topical fat removal Ingredients Exp.Example 1 Exp. Example 2 Exp. Example 3 Exp. Example 4 Comp. Example 1 Comp. Example 2 Comp. Example 3 Hyaluronidase 30,000 IU 30,000 IU 60,000 IU 30,000 IU 25,000 IU 65,000 IU - Lidocaine - 210 mg 210 mg 210 mg 210 mg - Peniramin - 12 mg 12 mg 12 mg 12 mg 12 mg - L-Carnitine - - 660 mg 660 mg 660 mg 660 mg - Vitamin C - - - 600 mg 600 mg 600 mg - Saline solution q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. 100 cc Total Amount (cc) 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100
  • the endomology treatment existing conventional treatment for edema, was carried out for four weeks, 30 sessions per week, with the decrease in waist circumference measured after one week and one month, and the results are shown in Table 4.
  • Example 3 Baseline (Day 0) 1 week after4 sessions Difference 1 month after 4 sessions Difference Comp.
  • Example 3 90.7 ⁇ 1.2 91.0 ⁇ 1.8 +0.3 ⁇ 1.2 90.5 ⁇ 1.3 -0.2 ⁇ 1.2
  • Example 1 91.0 ⁇ 1.0 89.4 ⁇ 0.4 -1.6 ⁇ 0.6 89.8 ⁇ 1.3 -1.2 ⁇ 0.3
  • Example 2 90.7 ⁇ 1.3 - - - - Exp.
  • Example 4 90.8 ⁇ 1.7 81.4 ⁇ 0.5 -9.4 ⁇ 0.2 81.3 ⁇ 0.3 -9.5 ⁇ 0.4 Endomology 92.0 ⁇ 2.0 89.8 ⁇ 1.4 -2.2 ⁇ 0.8 92.2 ⁇ 1.2 +0.2 ⁇ 1.5
  • the statistics package SPSS was used to obtain the distribution of measurements and the paired t-test was used to assess the effects of test injections on the decrease in waist circumference.
  • the analysis used a 95% confidence interval, adjusted for weight changes.
  • body fat analysis using the body fat analyzer Inbody showed an average fat loss of 1.5 to 2 kg.
  • Comparative Example 1 where 250 IU of hyaluronidase was administered [a total of 12500 IU administered for 50 points per round of treatment; a total of 4 rounds of treatment], the difference was -1.6 ⁇ 0.6 cm at one week after the treatment and -1.2 ⁇ 0.3 cm at one month after the treatment, showing a significantly inferior effect than the present invention.
  • Comparative Example 2 where 650 IU of hyaluronidase was administered [a total of 32500 IU administered for 50 points per round of treatment; a total of 4 rounds of treatment], the treatment was discontinued after the first session due to dimpling and bruising.
  • the injection composition of the present invention has been demonstrated to have an excellent effect in topical fat removal, with remarkably reduced side effects and no yo-yo effect.
  • the injection composition of the present invention has also been shown to have minimized side effects and an improved topical fat removal effect despite the use of a lower dose of hyaluronidase compared to the high dose hyaluronidase injection composition of the prior art KR 10-2009-0111916A.
  • Example 1 Redness Swelling Itching Pain above VAS 3 Bruise Dimpling Sagging Skin elasticity Comp.
  • Example 1 1 1 1 0 0 0 0 3 Comp.
  • Example 2 4 3 4 2 10 15 0 2 Comp.
  • Example 3 0 0 0 0 0 0 0 3 Exp.
  • Example 1 11 10 11 13 1 0 1 3 Exp.
  • Example 2 1 0 1 0 0 0 1 3 Exp.
  • Example 3 1 1 0 0 0 1 1 3 Exp.
  • Example 4 1 0 0 0 0 0 0 5
  • Reference Example 5 A skin muscle layer irradiating laser and its elasticity enhancing effect
  • a laser having a wavelength of 2940nm and set at a frequency of 3 Hz was used to irradiate the entire facial area from the oral mucosa toward the face for 5 minutes.
  • This laser treatment is painless, and provides a thermal effect to the oral mucosa in a non-ablative, non-invasive manner without anesthesia to give a remodeling and tightening effect.
  • the intraoral treatment of this step can lead to an instantaneous contraction of 30% of the tissue.
  • the instantaneous contraction of the upper dermis mechanically pulls up the underlying deeper tissue layers, creating a lifting effect.
  • this laser treatment delivers energy through the oral mucosa, it can protect the epidermis and stimulate collagen remodeling and neo-collagenesis (lasting up to 6 months).
  • this laser treatment has the advantage that it is accompanied by no bleeding or pain except some warmth felt in the oral mucosa and there is no down time since oral mucosa is particularly quick to recover.
  • the laser treatment was performed on 9 volunteers 5 times with an interval of one month.
  • peri-oral wrinkles significantly decreased in all of the volunteers.
  • the wrinkle score before treatment was 2.22 on the MFWS (Modified Fitzpatrick Wrinkle Scale)
  • the score after treatment was 0.69 on the MFWS, showing an about 69% decrease in the wrinkle index.
  • the present invention was conceived upon observing the effects of the treatments using A) a telomerase activating composition, B) a skin dermis irradiating laser, C) a composition for topical fat removal, and D) a skin muscle layer irradiating laser in the above Reference Examples.
  • A) a telomerase activating composition B) a skin dermis irradiating laser
  • C) a composition for topical fat removal and D) a skin muscle layer irradiating laser in the above Reference Examples.
  • the present inventor completed the present invention by experimentally ascertaining that synergistic effects are exhibited when the treatments with A) a telomerase activating composition, B) a skin dermis irradiating laser, C) a composition for topical fat removal, and D) a skin muscle layer irradiating laser are combined, compared to the effects observed in the individual steps in the above Reference Examples.
  • kits and aesthetic system for the prevention or treatment of skin aging 90 subjects were treated with different combinations based on A) a telomerase activating composition, B) a skin dermis irradiating laser, C) a composition for topical fat removal, and D) a skin muscle layer irradiating laser, the components of the kit and an aesthetic system for the prevention of skin aging according to the present invention, and the collagen production/contraction/remodeling effect; elasticity improvement effect; wrinkle improvement effect; topical fat removal and facial contouring effect; telomerase activating effect; skin tone improvement effect; satisfaction and side effects were determined. Details of the study are described below.
  • the subjects included in the present study were those who i) were informed of the purpose and study overview, procedures of the study and the requirements of the protocol, and signed an informed consent form. ii) were healthy, having no acute or chronic diseases including skin diseases, and iii) could be followed up during the study period.
  • the subjects were randomized into groups and treated with different combinations of the components of the kit and aesthetic system of the present invention, (A), (B), (C), and (D).
  • telomerase activating composition 3 cc of a telomerase activating composition containing 0.00056%(w/w) of a Kappaphycus alvarezii extract was applied, followed by irradiation with Legato (Alma Lasers, Israel), an ultrasound laser facilitating the deep penetration of cosmetics by ultrasound vibration, at a frequency of 30 Hz and 50% of maximum power output for 10 minutes over the entire face area in 1 to 2 passes.
  • composition for topical fat removal comprising a hyaluronidase: 100 cc of a composition for topical fat removal comprising 30,000 IU of hyaluronidase, 210 mg of lidocaine, 12 mg of Peniramin, 660 mg of L-carnitine, and 600 mg of vitamin-C, identical to Experimental Example 4 of Reference Example 4 described above, was prepared and a volume of 1 cc each, comprising 300 IU of hyaluronidase, was injected at 10 points with an interval between injection points of 1 cm.
  • Treatments for subject groups Treatments Control 1 A Control 2 B Control 3 C Control 4 D Control 5 A + B + C Control 6 A + B + D Control 7 A + B + C Control 8 B + C + D Test group A + B + C + D
  • the collagen production/contraction/remodeling effect, skin elasticity enhancement effect, wrinkle improvement effect, facial contouring effect resulting from topical fat removal, topical fat removal/lipolysis in adipose cells/reduction of edema, telomerase activation in skin cells, and skin tone improvement effect were determined over time.
  • the skin biopsy specimens of the study subjects were collected to measure the number of collagen fibers. Specifically, skin biopsy specimens were fixed in 2.5% glutaraldehyde solution, washed with 0.1 M phosphate buffer (pH 7.4), and post-fixed in 1% osmium tetroxide solution for 2 hours. Next, the skin tissue was dehydrated with graded ethyl alcohol from 50% to anhydrous alcohol, infiltrated with propylene oxide, and then embedded in an Epon resin mixture. Thin survey sections with 1 ⁇ m thickness were cut to select areas of interest, and then ultrathin sections were obtained and treated with tannic acid to enhance the resolution of collagen fibers, followed by conventional double staining with uranyl acetate and lead citrate.
  • the test group according to the present invention (treated with the combination A, B, C, and D) showed a better collagen fiber increasing effect than all control groups from 1 week to 4 weeks after the treatment.
  • the test group showed a superior, synergistic effect (4 weeks post-treatment: 127.0%).
  • the test group showed a better effect than the sum of the effects found in the group treated with the combination ABC and a single treatment group treated with D (4 weeks post-treatment: 61.4%), the sum of the effects found in the group treated with the combination ABD and a single treatment group treated with C (4 weeks post-treatment: 61.4%), the sum of the effects found in the group treated with the combination ACD and a single treatment group treated with B (4 weeks post-treatment: 65.6%), and the sum of the effects found in the group treated with the combination BCD and a single treatment group treated with A (4 weeks post-treatment: 57.5%).
  • the aesthetic kit and aesthetic system of the present invention exhibited an excellent synergistic effect in increasing the number of collagen fibers.
  • the skin elasticity of the study subjects was determined. Specifically, DermaLab USB elasticity probe (Cortex Technology, Inc.) was employed to evaluate the skin elasticity improvement in the study subjects.
  • the DermaLab USB elasticity probe indicates the changes in the skin and the force of restoration due to the suction and duration of suction at the area of interest.
  • the probe of the device was glued to the left cheek of test subjects using a special tape before taking the measurements. Considering that repeated measurements at the same site cause an elevated level of fatigue in the skin, each site of elasticity measurement was used only once. Changes in skin elasticity were analyzed using an application software (version 1.09) that is an exclusive analysis program for DermaLab USB.
  • Young's modulus (E) was used for the analysis, with a greater Young's modulus (E) indicating a higher elasticity.
  • Young's modulus (E) is a value based on the deference of force needed when the skin surface is elevated 1.5 mm, the distance between two infrared detection lines in the measuring probe, and its unit of measurement is MegaPascal(MPa).
  • the elasticity measurements were taken before treatment (baseline), as well as 1 week, 2 weeks, 3 weeks, and 4 weeks after treatment. The results are summarized in Table 8, and illustrated in FIG. 10 using a graph.
  • the test group according to the present invention (treated with the combination A, B, C, and D) showed a better skin elasticity improvement effect than all control groups from 1 week to 4 weeks after the treatment. Particularly, compared to the sum of the skin elasticity improvement effects in the single treatment groups, treated with A, B, C, or D (4 weeks post-treatment: elasticity improvement 46.01%), the test group showed a superior effect (4 weeks post-treatment: 81.50%).
  • test group showed a better effect than the sum of the effects found in the group treated with the combination ABC and a single treatment group treated with D (4 weeks post-treatment: 48.56%), the sum of the effects found in the group treated with the combination ABD and a single treatment group treated with C (4 weeks post-treatment: 36.35%), the sum of the effects found in the group treated with the combination ACD and a single treatment group treated with B (4 weeks post-treatment: 47.25%), and the sum of the effects found in the group treated with the combination BCD and a single treatment group treated with A (4 weeks post-treatment: 47.82%).
  • the kit and aesthetic system of the present invention for the prevention of skin aging exhibit an excellent synergistic effect in skin elasticity improvement.
  • the wrinkle improvement effect in the study subjects were determined.
  • a device quantifying the extent of wrinkling (Aramo TS, programmed by Aram HUVIS Co., South Korea) was used.
  • the head of a Beauty scope (x10 lens) with a diameter of 30 mm was placed in close contact with the skin surface of the area of interest, and pressed perpendicularly onto the skin with constant pressure. Then, differences in the brightness of the skin generated by the light from the device head were used to quantify the wrinkling.
  • a negative model of skin wrinkles thus obtained can be transformed into a positive format using a software, or parameter values can be adjusted for diverse measurement lines.
  • As for the extent of wrinkling a value of 10 ⁇ 12 indicates normal wrinkling for people in their twenties. The results are summarized in Table 9, and illustrated in FIG. 11 using a graph.
  • the test group according to the present invention (treated with the combination A, B, C, and D) showed a better wrinkle improvement effect than all control groups from 1 week to 4 weeks after the treatment.
  • the test group showed a superior, synergistic effect (4 weeks post-treatment: -6.81).
  • the test group showed a better effect than the sum of the effects found in the group treated with the combination ABC and a single treatment group treated with D (4 weeks post-treatment: -3.67), the sum of the effects found in the group treated with the combination ABD and a single treatment group treated with C (4 weeks post-treatment: -2.94), the sum of the effects found in the group treated with the combination ACD and a single treatment group treated with B (4 weeks post-treatment: -3.90), and the sum of the effects found in the group treated with the combination BCD and a single treatment group treated with A (4 weeks post-treatment: -2.74).
  • the kit and aesthetic system of the present invention for the prevention of skin aging have an excellent synergistic effect in wrinkle improvement.
  • Example 4 Assessment of the skin contouring effect resulting from topical fat removal and reduction of edema
  • the skin contouring effect resulting from the administration of a composition for topical fat removal etc. was determined in the study subjects. Specifically, ultrasound was used to measure the thickness of subcutaneous fat in the face area of study subjects. A SuperSonic Imagine (Les Jardins de la Duranne, Aix en Brussels, France) device was used for the ultrasound based measurement. The tester and the subject sat facing each other to measure the thickness of subcutaneous fat in the cheek and chin areas, and the pressure on the ultrasound device was minimized to correctly measure the thickness. An aqueous gel was applied to the site of measurement to help transmit the ultrasound, and a high frequency linear probe at 6.0-MHz was used to take measurements at the two sites, followed by calculation of the average value. The results are summarized in Table 10, and illustrated in FIG. 12 using a graph.
  • the test group according to the present invention (treated with the combination A, B, C, and D) showed an excellent fat thickness reducing effect from 1 week to 4 weeks after the treatment. It can be seen that this effect depends on the inclusion of the treatment with C (a composition for topical fat removal), an element of the present invention, and a prominent synergistic effect can be observed from 1 week after treatment, which lasts until 4 weeks after treatment.
  • telomerase activation was assessed in the study subjects.
  • the study subjects abstained from caffeine, excessive medication or metabolism regulators for 24 hours before their blood test, and blood samples were drawn at 10 AM after they took enough rest.
  • a sandwich enzyme immunoassay was used to measure the amount of telomerase in the samples. Specifically, a standard or test specimen containing telomerase was applied to a plate coated with a monoclonal antibody (MAb) specific to telomerase (TA), thereby attaching telomerase to the plate.
  • MAb monoclonal antibody specific to telomerase
  • an HRP (horseradish peroxidase) conjugated polyclonal antibody that specifically binds to telomerase is prepared and applied to the plate, resulting in its binding to the telomerase associated with the plate, in a sandwich-like format.
  • HRP horseradish peroxidase conjugated polyclonal antibody that specifically binds to telomerase
  • telomerase activity improvement Average telomerase activity in each group Baseline 1 week post-treatment 2 weeks post-treatment 3 weeks post-treatment 4 weeks post-treatment Control 1 -A 0.30 ⁇ 0.23 1.28 ⁇ 0.23 1.29 ⁇ 0.14 1.30 ⁇ 0.78 1.31 ⁇ 0.46 Control 2 -B 0.31 ⁇ 0.58 0.31 ⁇ 0.25 0.31 ⁇ 0.11 0.32 ⁇ 0.64 0.32 ⁇ 0.21 Control 3 -C 0.42 ⁇ 0.24 0.42 ⁇ 0.49 0.42 ⁇ 0.46 0.42 ⁇ 0.24 0.42 ⁇ 0.11 Control 4 -D 0.45 ⁇ 0.16 0.45 ⁇ 0.65 0.46 ⁇ 0.77 0.45 ⁇ 0.31 0.46 ⁇ 0.14 Control 5 -ABC 0.35 ⁇ 0.68 1.13 ⁇ 0.27 1.21 ⁇ 0.54 1.29 ⁇ 0.29 1.36 ⁇ 0.41 Control 6 -ABD 0.36 ⁇ 0.42 1.20 ⁇ 0.81 1.23 ⁇ 0.16 1.28 ⁇ 0.64 1.37 ⁇ 0.32 Control 7 -ACD 0.44 ⁇ 0.28 1.23 ⁇ 0.46 1.31 ⁇ 0.94 1.38 ⁇ 0.55 1.42 ⁇ 0.27 Control 8 -
  • the test group according to the present invention (treated with the combination A, B, C, and D) showed a better telomerase activating effect than all control groups from 1 week to 4 weeks after the treatment.
  • the test group showed a superior, synergistic effect (4 weeks post-treatment: 1.20).
  • the test group showed a better, synergistic effect than the sum of the effects found in the group treated with the combination ABC and a single treatment group treated with D (4 weeks post-treatment: 1.02), the sum of the effects found in the group treated with the combination ABD and a single treatment group treated with C (4 weeks post-treatment: 1.01), the sum of the effects found in the group treated with the combination ACD and a single treatment group treated with B (4 weeks post-treatment: 0.99), and the sum of the effects found in the group treated with the combination BCD and a single treatment group treated with A (4 weeks post-treatment: 1.01).
  • the kit and aesthetic system of the present invention for the prevention of skin aging have an excellent effect on telomerase activation.
  • the skin hydration of the study subjects was determined. This is done by measuring the capacitance reflecting the content of water, which has the highest dielectric constant in the skin, indicated by an arbitrary unit (AU). That is, skin hydration is usually determined by measuring the capacitance of the weak current transmitted to a probe contacting the skin surface. As the water content and capacitance are proportional to each other, the greater the skin hydration, the higher the measurement values are.
  • This measuring device thus can consistently measure the water content within the depth of 30 ⁇ 40 ⁇ m underneath the stratum corneum under a condition that is not substantially affected by the application of cosmetics or medications (conductor track in electric scatter field).
  • the device has a unique capacity to assess skin hydration under special test conditions, e.g., when the probe is maintaining a slight distance from the skin without directly contacting it.
  • the readings of the device range from a minimum of 0 AU to 120 AU.
  • the capacitance of a solid is generally 7 F (farad), and the capacitance of water is 81 F. Then, if a weak current between 7 F and 81 F flows, differences in the capacitance will appear. This difference is divided by 120 to give the values of the above arbitrary unit (AU).
  • plastics which generally do not contain any water are shown to have a capacitance of about 6 ⁇ 8 AU when measured by the device, and 100 % moisture would give 120 AU when measured. That is, a higher value is interpreted to indicate a higher water content.
  • a numerical reading appears when a probe with a diameter of 16 mm was placed at the site of measurement in close contact with the skin surface and pressed perpendicularly onto the skin with a constant pressure, and the average of 5 measurements taken within a certain area (central region between the cheek bone and chin, 4 x 4 cm) was used for the record.
  • a reading of 35 ⁇ 40 indicates a good degree of hydration
  • 31 ⁇ 34 indicates a slight lack of moisture
  • 25 ⁇ 30 indicates a moisture-lacking condition.
  • the test group according to the present invention (treated with the combination A, B, C, and D) showed a better skin hydration improvement effect than all control groups from 1 week to 4 weeks after the treatment.
  • the test group showed a superior, synergistic effect (4 weeks post-treatment: 7.39).
  • the test group showed a better, synergistic effect than the sum of the effects found in the group treated with the combination ABC and a single treatment group treated with D (4 weeks post-treatment: 2.71), the sum of the effects found in the group treated with the combination ABD and a single treatment group treated with C (4 weeks post-treatment: 3.56), the sum of the effects found in the group treated with the combination ACD and a single treatment group treated with B (4 weeks post-treatment: 2.32), and the sum of the effects found in the group treated with the combination BCD and a single treatment group treated with A (4 weeks post-treatment: 2.61).
  • the kit and aesthetic system of the present invention for the prevention of skin aging have an excellent effect in skin hydration improvement.
  • the test group according to the present invention (treated with the combination A, B, C, and D) showed a better skin roughness reducing effect than all control groups from 1 week to 4 weeks after the treatment.
  • the test group showed a superior, synergistic effect (4 weeks post-treatment: -3.82).
  • the test group showed a better, synergistic effect than the sum of the effects found in the group treated with the combination ABC and a single treatment group treated with D (4 weeks post-treatment: -2.55), the sum of the effects found in the group treated with the combination ABD and a single treatment group treated with C (4 weeks post-treatment: -2.21), the sum of the effects found in the group treated with the combination ACD and a single treatment group treated with B (4 weeks post-treatment: -1.75), and the sum of the effects found in the group treated with the combination BCD and a single treatment group treated with A (4 weeks post-treatment: -3.56).
  • the kit and aesthetic system of the present invention for the prevention of skin aging have an excellent, synergistic effect in skin roughness reduction.
  • RSA Robot Skin Analyzer CS 50, In Forward. Inc., Japan
  • RSA is an instrument that allows for a combined examination of pores, pigmentation, wrinkles, skin tone, etc. It can take photographs from an identical angle and lighting by using the Compact booth, and has a high reproducibility.
  • the pores and changes in the amount of pigmentation in the study subjects were measured with this instrument, which, consisting of two parts, an image capturing device and an image analyzing computer system, captures the image information on wrinkles, pigment, skine tone, pores, etc. and directly produces the results. It enables an accurate analysis as it can take photographs from three different angles.
  • Table 14 The results are summarized in Table 14, and illustrated in FIG. 16 using a graph.
  • Pigmentation reduction (%) Average pigmentation reduction in each group (%) 1 week post-treatment 2 weeks post-treatment 3 weeks post-treatment 4 weeks post-treatment Control 1 -A -1.22 -1.26 -1.54 -1.64 Control 2 -B -1.19 -1.28 -1.42 -1.54 Control 3 -C -0.01 -0.02 -0.01 -0.13 Control 4 -D -1.02 -1.04 -1.10 -1.11 Control 5 -ABC -2.00 -2.11 -2.24 -2.28 Control 6 -ABD -3.13 -3.47 -3.55 -3.96 Control 7 -ACD -1.65 -1.56 -1.66 -1.84 Control 8 -BCD -1.26 -1.33 -1.52 -1.62 Test group -ABCD -4.25 -4.22 -4.48 -4.58
  • the test group according to the present invention showed a better pigmentation reducing effect than all control groups from 1 week to 4 weeks after the treatment.
  • the test group showed a prominently superior, synergistic effect (4 weeks post-treatment: -4.58) than the sum of the effects found in the group treated with the combination ABC and a single treatment group treated with D (4 weeks post-treatment: -3.39), the sum of the effects found in the group treated with the combination ABD and a single treatment group treated with C (4 weeks post-treatment: -3.83), the sum of the effects found in the group treated with the combination ACD and a single treatment group treated with B (4 weeks post-treatment: -3.38), and the sum of the effects found in the group treated with the combination BCD and a single treatment group treated with A (4 weeks post-treatment: -3.26).
  • the kit and aesthetic system of the present invention for the prevention of skin aging
  • Example 7 Evaluation questionnaire for post-treatment changes in the skin and satisfaction, and side effects
  • An evaluation questionnaire survey was conducted with respect to the post-treatment changes in the skin and satisfaction of the study subjects at 4 weeks after treatment.
  • the questionnaire consisted of 8 questions, including 7 questions on the evaluation of satisfaction on the changes in the skin and 1 question on the intention to use in the future, to the survey subjects' self-assessment after treatment.
  • the study areas were observed for adverse skin reactions such as erythema, edema, scaling, itching, and prickling, and the results are summarized in Table 15.
  • the kit or aesthetic system for the prevention of skin aging according to the present invention got the highest satisfaction for all self-assessment of effect items.
  • kits or aesthetic system for the prevention of skin aging according to the present invention has synergistic effects in various aspects related to skin aging, by virtue of comprising the components A, B, C, and D. Accordingly, 80% of the subjects in the group treated with the combination ABCD, the kit for the prevention of skin aging according to the present invention, indicated a strong intention to use in the future, while less than 30% of the subjects in the control groups indicated an intention to use in the future.

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Abstract

L'invention concerne un kit et un système esthétique de prévention contre le vieillissement de la peau comprenant une composition d'activation de la télomérase, un laser d'exposition de derme cutané à un rayonnement, une composition d'élimination de graisse topique comprenant une hyaluronidase, et un laser d'exposition de couche de muscle cutané à un rayonnement, ainsi qu'une méthode de prévention contre le vieillissement de la peau chez des êtres humains à l'aide dudit kit et dudit système. Le kit et le système esthétique destinés à la prévention contre le vieillissement de la peau ont des effets étendus concernant le vieillissement de la peau, y compris une amélioration instantanée des rides, un modelage de la peau, une amélioration de l'élasticité, une amélioration des rides, une élimination de graisse topique et une amélioration d'hydratation cutanée ainsi que des effets d'entretien de longue durée allant jusqu'à 1 an à 1,5 an, malgré leur court temps de traitement.
PCT/KR2018/001019 2017-01-25 2018-01-23 Kit et système esthétique de prévention contre le vieillissement de la peau WO2018139835A1 (fr)

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WO2022073664A1 (fr) 2020-10-09 2022-04-14 Gelita Ag Hydrolysat de collagène utilisé en tant que substance active pour retarder le vieillissement

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